Wasps scored with the final play of the game to shatter Saints' hopes of a superb Aviva Premiership away victory.
Jim Mallinder's men had produced a blistering attack display, scoring five tries in the Ricoh Arena sunshine.
But, with the clock having hit 80 minutes, prop Matt Mullan drove over and Jimmy Gopperth converted to give Wasps an incredible 32-30 victory.
Saints had played so well for so long, pushing forward with real vigour.
They were 18-13 up at half-time thanks to tries from Ben Foden, Alex Waller and George North.
But Stephen Myler had a tough time kicking in the swirling wind, with the fly-half missing several tricky kicks.
And Wasps, who have not lost a league game at home since December 2015, were to go ahead after the break as they scored twice early in the second period.
Saints stormed back with tries from the impressive Ahsee Tuala and replacement Teimana Harrison, but Mullan had the final say as Mallinder's men lost in agonising fashion.
They did walk away with two points, thanks to a losing bonus point and a try bonus point, but they will have felt they could have had three more.
As it is, they must now move on to face Saracens at Stadium MK next Sunday with their top-six hopes still in the balance.
Early on at the Ricoh Arena, Saints had switched North and Foden so that the big Wales wing could go up against Wasps flyer Christian Wade.
But it was Foden who nearly scored as Josh Bassett dallied on grabbing a bouncing ball and just managed to smuggle it into touch as the Saints man closed in at speed.
Saints missed a clearer chance to go ahead soon after as Myler spurned a penalty chance that he would normally expect to make.
But Myler soon made amends as the sloppy start from the home side and the slick opening from the away team continued.
Wasps were really struggling to get going, with their clearances poor and their passing errant.
And Saints were soon making them pay again as Foden intercepted a Gopperth pass on halfway and showed good speed to race in to dot down in the corner.
Myler missed the tricky touchline conversion and Wasps responded as they found a gaping hole in the Saints defence for Elliot Daly to glide through and score.
Gopperth added the extras to cut the gap to a point, but Saints were soon back on the front foot with some sumptuous offloads from full-back Tuala and Nic Groom putting pressure on.
And it wasn't long before Saints scored their second try as some rapid build-up play ended with scrum-half Groom sending Alex Waller over in the corner.
Myler again missed the tough touchline conversion and Gopperth responded by landing a couple of penalties at the other end to level the scores.
Gopperth had the chance to put his team ahead with another penalty, but this time saw his effort rebound off the left post.
Saints would have been unfortunate to be behind at the break, and, as it turned out, they would go back ahead before the interval.
Tuala again broke away and after some rapid play from right to left, a fantastic offload from Harry Mallinder set up North for the score in the corner.
Myler again missed the conversion to complete his difficult first half with the boot.
Saints needed a strong start to the second half to consolidate their lead, but they got the opposite thanks to wing wizard Wade.
The diminutive wide man saw space to chip over the Saints defence and used his speed to easily win the race, gather and score.
Gopperth converted to put Wasps ahead for the first time and the home side were suddenly rampant, running at Saints from all angles.
And it wasn't long before another try came as scrum-half Joe Simpson picked the ball up five metres out and found a small gap to stretch an arm out to score.
Gopperth missed the conversion, but Saints were now seven points behind and needed to summon a response.
And they did, using a five-metre scrum to set up a score for the lively Tuala out wide.
But again the conversion went astray as Myler was forced to kick from the touchline in the wind once more.
However, he was to finally have an easy effort 10 minutes from time as Fiji lock Api Ratuniyarawa offloaded superbly to fellow replacement Harrison, who stormed through the middle to score.
Saints were five points up with 12 minutes to go, but it looked like Wasps had responded immediately as Willie Le Roux went over.
However, referee Craig Maxwell-Keys went to the TMO and spotted that Joe Launchbury had obstructed Luther Burrell in the build-up and Saints were given a penalty.
But after wave after wave of pressure, Wasps were to break Saints hearts before the end as Mullan popped up to drive over.
Gopperth converted with the final kick of the game to bring a roar from the home fans, who waved their flags furiously as Saints saw their hopes of a vital victory go up in smoke.
Wasps: Le Roux; Wade, Daly, Beale, Bassett; Gopperth, Simpson (Robson 53); Mullan, Taylor (Cruse 64), Swainston (Doran-Jones 61); Launchbury (c), Myall (Symons 56); Johnson (Hughes 46), Young, Thompson.
Saints: Tuala (K Pisi 72); North, Tuitavake (Burrell 64), Mallinder, Foden; Myler, Groom (Dickson 66); A Waller (E Waller 66), Hartley (Haywood 61), Brookes (Hill 53); Lawes, Ribbans (Ratuniyarawa 68); Gibson, Wood (c) (Harrison 61), Picamoles.
Referee: Craig Maxwell-Keys